Analysis of the peripheral T-cell repertoire in kidney transplant patients.

The long-term stability of renal grafts depends on the absence of chronic rejection. As T cells play a key role in rejection processes, analyzing the T-cell repertoire may be useful for understanding graft function outcomes. We have therefore investigated the power of a new statistical tool, used to analyze the peripheral blood TCR repertoire, for determining immunological differences in a group of 229 stable renal transplant patients undergoing immunosuppression. Despite selecting the patients according to stringent criteria, the patients displayed heterogeneous T-cell repertoire usage, ranging from unbiased to highly selected TCR repertoires; a skewed TCR repertoire correlating with an increase in the CD8(+) /CD4(+) T-cell ratio. T-cell repertoire patterns were compared in patients with clinically opposing outcomes i.e. stable drug-free operationally tolerant recipients and patients with the "suspicious" form of humoral chronic rejection and were found significantly different, from polyclonal to highly selected TCR repertoires, respectively. Moreover, a selected TCR repertoire was found to positively correlate with the Banff score grade. Collectively, these data suggest that TCR repertoire categorization might be included in the calculation of a composite score for the follow-up of patients after kidney transplantation.

Statistical analysis of CDR3 length distributions for the assessment of T and B cell repertoire biases.

Complementarity-determining region 3 (CDR3) length distribution analysis explores the diversity of the T cell receptor (TCR) and immunoglobulin (Ig) repertoire at the transcriptome level. Studies of the CDR3, the most hypervariable part of these molecules, have been frequently used to identify recruitment of T and B cell clones involved in immunological responses. CDR3 length distribution analysis gives a clear perception of repertoire variations between individuals and over time. However, the complexity of CDR3 length distribution patterns and the high number of possible repertoire alterations per individual called for the development of robust data analysis methods. The goal of these methods is to identify, quantify and statistically assess differences between repertoires so as to offer a better diagnostic or predictive tool for pathologies involving the immune system. In this review we will explain the benefit of analyzing CDR3 length distribution for the study of immune cell diversity. We will start by describing this technology and its associated data processing, and will subsequently focus on the statistical methods used to compare CDR3 length distribution patterns. Finally, we will address the various methods for assessing CDR3 length distribution gene signatures in pathological states.

[History and uses of honey, mead and hive products]. / Histoire et emplois du miel, de l'hydromel et des produits de la ruche.

From Antiquity to marketing of cane sugar, and beet sugar in particular, honey was greatly consumed for its sweetening power; it was also employed for its therapeutic properties. Actually, it is always used in feeding and dietetic, and only as popular remedy. The hive products: pollen, propolis, royal jelly, introduced for few decades in dietetic meet show a great commercial passion; the beeswax was excipient in beauty care. These different aspects are developed in this study.

Amatoxin poisoning treatment decision-making: pharmaco-therapeutic clinical strategy assessment using multidimensional multivariate statistic analysis.

Ninety percent of fatal higher fungus poisoning is due to amatoxin-containing mushroom species. In addition to absence of antidote, no chemotherapeutic consensus was reported. The aim of the present study is to perform a retrospective multidimensional multivariate statistic analysis of 2110 amatoxin poisoning clinical cases, in order to optimize therapeutic decision-making. Our results allowed to classify drugs as a function of their influence on one major parameter: patient survival. Active principles were classified as first intention, second intention, adjuvant or controversial pharmaco-therapeutic clinical intervention. We conclude that (1) retrospective multidimensional multivariate statistic analysis of complex clinical dataset might help future therapeutic decision-making and (2) drugs such as silybin, N-acetylcystein and putatively ceftazidime are clearly associated, in amatoxin poisoning context, with higher level of patient survival.

Changes in stone composition according to age and gender of patients: a multivariate epidemiological approach.

Urinary stone incidence and composition have changed markedly over the past half-century in industrialized countries, in parallel with profound changes in living standards and dietary habits, with a dramatic increase in the incidence of calcium oxalate stones. However, studies evaluating the influence of age and gender on the distribution of the various types of urinary calculi are scarce. We report the results of a study based on 27,980 calculi (from 19,442 males and 8,538 females) analyzed by infrared spectroscopy between 1976 and 2001. The relationships between age and sex and stone composition were investigated using a multivariate approach, based on correspondence factor analysis (CFA). We found a male predominance for calcium oxalate and uric acid, a female preponderance for calcium phosphate and struvite stones, and an increasing prevalence of uric acid stones with age in both genders. CFA was able to reconstruct in blind the age curve from stone composition. The first two axes of the multidimensional classification, which correspond to age, included 86.9% of the total variance, indicating that age was the main factor involved in stone type. Superimposition of age classes and stone components showed a strong relationship between age and whewellite, weddellite, brushite, carbapatite, octacalcium phosphate and uric acid, while other substances (whitlockite, amorphous carbonated calcium phosphate, struvite, proteins, mucopolysaccharides, triglycerides or ammonium urate) appeared weakly related to age. In addition, CFA suggests the role of common lithogenic factors between weddellite, carbapatite and brushite, which clustered in the same area, whereas the various crystalline forms of phosphate stones segregated into two different clusters, suggesting distinct pathogenic factors. In conclusion, this study provides a picture of the present epidemiology of urinary stones in France. CFA helped to confirm: (1) an etiopathogenic distinction between weddellite and whewellite, (2) etiopathogenic associations between chemical compounds, which were only suspected on a clinical basis, and (3) suggested yet unrecognized associations, especially with respect to the heterogeneous group of phosphate stones.

Using the volumetric indices of telencephalic structures to distinguish Salamandridae and Plethodontidae: comparison of three statistical methods.

The aim of this study was to establish whether appropriate statistical analysis of 16 volumetric indices corresponding to 16 structures making up the entire telencephalon of Urodela could distinguish between two families, Salamandridae and Plethodontidae. We compared the efficiency of three statistical methods (stepwise discriminant analysis, artificial neural networks, correspondence factor analysis) and the information they provide. All three methods found the same species difficult to classify. However, only correspondence factor analysis could suggest explanations for "misclassifications" as it superimposes the two sets of variables, (sub)species and anatomical variables, thus revealing the correlations between them. The bulbus olfactorius accessorius and the caudal mitral cell layer of the bulbus olfactorius principalis were the most discriminatory structures in separating Salamandridae and Plethodontidae. The correspondence factor analysis mapped species very much in line with accepted taxonomy and highlighted several current controversies [e.g. positioning of certain newts (T. marmoratus, T. vulgaris, T. alpestris), of Salamandrina terdigitata, and of members of the genus Euproctus]. Mapping of Plethodontidae was less clear-cut than that of Salamandridae with more overlap among genera but was quite consistent with knowledge of brain structure complexification. We conclude that relationships derived from analyses of telencephalic structures provide valuable information that might help resolve ambiguities; we have coined the term "neurotaxonomy" for this approach.

A comparative study of sex pheromone reception in the Hadeninae (Lepidoptera: Noctuidae).

Abstract A comparative study of the olfactory responses to pheromone compounds was performed in twenty-four species of Hadeninae. Electroantennograms (EAG) were recorded on male moths in response to thirty compounds and the response profiles of each species were analysed by factorial correspondence analysis. A limited number of molecules were found active and the most effective stimuli were Z9 tetradecenes and Z11 hexadecenes. The species of the Mythimna genus were most sensitive to aldehydes. Tholera decimalis did not respond to any of the molecules tested. The species belonging to the Mamestra and the Orthosia genera responded to a variety of molecules and no simple correlation was found between the genus and the EAG sensibility. Pheromone reception is discussed in relation to the taxonomy and the evolution of olfactory communication in Hadeninae.

Different patterns of TCR beta chain regulation following allo- and xeno-transplantation.

BACKGROUND: In the concordant hamster-to-rat cardiac xenograft model, recipients treated with cobra venom factor for the first 10 days following transplantation and daily with Cyclosporine A (CsA) do not reject their grafts. However, when CsA is withdrawn on day 40, an acute cellular rejection occurs within 4 +/- 1 days. Allografts performed in the same conditions are rejected within 18 +/- 4 days. METHODS: In this model, we have compared graft infiltrating T cells through both a quantitative (number of Vbeta transcripts) and qualitative (CDR3 length distribution) assessment of the T cell receptor (TCR) beta chain transcriptome in allo- and xeno-transplantations. RESULTS: We report striking differences in TCR usage at day 15 following allo- and xeno-transplantation as well as during rejection following CsA withdrawal. The number of Vbeta transcripts was high in both rejected allo- and xenografts. However, whereas in xenografts acute rejection occurred without skewing of Vbeta CDR3 length distribution, T cells infiltrating allografts during rejection after CsA interruption had a highly altered CDR3 length distribution pattern. In addition, using a correspondence factor analysis of the beta chain transcriptome, we show that some families can clusterize and can discriminate allo- or xeno-patterns at the level of both the number of Vbeta transcripts and the CDR3 length distribution. CONCLUSIONS: Our data show that, in vivo, even in the hamster-to-rat concordant combination, the anti-xenograft T cell response is strong and will likely represent another challenge for xenotransplantation.